Results

The majority of patients were characterized by the presence of comorbidities and the
absence of immunosuppressive conditions. pH1N1 specific antibody production was observed
around day 9 from disease onset and defined an early period of innate immune response
and a late period of adaptive immune response to the virus. The most severe patients
(n = 12) showed persistence of viral secretion. Seven of the most severe patients died.
During the late phase, the most severe patient group had impaired expression of a
number of genes participating in adaptive immune responses when compared to less severe
patients. These genes were involved in antigen presentation, B-cell development, T-helper
cell differentiation, CD28, granzyme B signaling, apoptosis and protein ubiquitination.
Patients with the poorest outcomes were characterized by proinflammatory hypercytokinemia,
along with elevated levels of immunosuppressory cytokines (interleukin (IL)-10 and
IL-1ra) in serum.

Conclusions

Our findings suggest an impaired development of adaptive immunity in the most severe
cases of pandemic influenza, leading to an unremitting cycle of viral replication
and innate cytokine-chemokine release. Interruption of this deleterious cycle may
improve disease outcome.